Arginine vasopressin is synthesized in the hypothalamic area and is a peptide composed of 9 amino acids, which is excreted from the posterior pituitary. Receptors of arginine vasopressin are classified into three kinds of subtypes of V1a, V1b, and V2, a V1a receptor exists in the liver, muscular tissue vascular cells, blood platelets, peripheral tissues, and central nerve system, a V1b receptor exists in the central nerve system, and a V2 receptor exists in the kidney collecting tubule cells. When arginine vasopressin is connected to a V2 receptor, reabsorption of water is promoted in the kidney collecting tubule and a urinary volume is decreased. Therefore, when arginine vasopressin is in short, polyuria is caused, and examples of diseases due to polyuria include central diabetes insipidus, childhood nocturnal enuresis, nocturia, and overactive bladder. Accordingly, a V2 receptor agonist is useful as a preventive or therapeutic agent of these diseases. In addition, a V2 receptor agonist has release actions of a blood VIII factor and a Von Willebrand factor and can thus treat hemorrhagic diseases (such as hemophilia and Von Willebrand disease).
Conventionally, desmopressin that is a peptide (arginine vasopressin in which an amino group of the 1st cysteine is deleted and the 8th arginine is converted into d type) has been used for treatments of central diabetes insipidus and nocturnal enuresis as a V2 receptor agonist. However, an oral agent of desmopressin is very low in a biological availability and a high dosage is required in order to attain its effects. Furthermore, a preparation of desmopressin is expensive, also, there is a concern about occurrence of side effects caused by fluctuation of absorption among individuals, and a preparation of desmopressin is not necessarily satisfied in view of safety. Accordingly, creation of a medical drug having a high biological availability and less fluctuation of absorption has been desired.
On the other hand, a metabolic reaction due to cytochrome P-450 (CYP) plays a dominant role in disappearance of a drug from a body, and when a drug metabolized by CYP having the same molecular species competes against each other in the metabolic enzyme, some sort of metabolic inhibition is assumed to be caused. Inhibition of CYP may lead to variation in a blood concentration and a tissue concentration of a drug, change in treatment effects, and occurrence of serious side effects. Therefore, creation of a medical drug having low affinity to CYP and less concern about enzymatic inhibition has been desired.
So far, benzoheterocyclic derivatives (Patent Literatures 1 to 3), benzoazepine derivatives (Patent Literatures 4 and 5), an amide derivative (Patent Literature 6), a benzodiazepine derivative (Patent Literature 7) have been reported as a compound having a vasopressin receptor agonistic action, and a substituted spiro benzoazepine derivative (Patent Literature 8) has been reported as a compound having a vasopressin receptor antagonistic action; however, these compounds are different from the compound of the present application in the structure having a carbonyl group on the 4th carbon of benzoazepine.